177657-05-5Relevant articles and documents
Synthesis and stereoselective C-C bond-forming reactions of peptide aldehydes
Reetz, Manfred T.,Griebenow, Nils
, p. 335 - 348 (2007/10/03)
The reaction of the activated form of N-protected amino acids 6 and 10 or peptides 14 and 18 with chiral amino alcohols derived from the corresponding α-amino acids affords peptide alcohols which can be oxidized under Swern conditions to produce the corresponding peptide aldehydes 9, 12, 16 and 20. The rational synthesis of diastereomeric di- and tripeptide aldehydes, e.g., (S,S)- or (R,S)-dipeptides as well as (S,S,S)- or (R,S,S)-tripeptides is possible by proper choice of the respective building blocks [(S)- versus (R)-amino acids]. The compounds can be prepared without any undesired α-epimerization. However, the long-term configurational stability depends upon the configuration at the remote stereogenic center, e.g., (R,S)-dipeptide aldehydes epimerize faster than the (S,S) diastereomers. Di- and tripeptide aldehydes 9, 12, 16 and 20 undergo chelation-controlled Grignardtype additions with Me2CuLi that involve little or no undesired α-epimerization. The (S,S)- and (R,S)-dipeptide aldehydes 9 and 12 undergo chelation-controlled pinacol reactions induced by the low-valent vanadium reagent [V2Cl3(THF)6]2[Zn2Cl 6]. The major products in both cases are the corresponding C2-symmetric diols 33 and 36, respectively, which are of interest as potential HIV-protease inhibitors. The degree of stereoselectivity is significantly higher in the case of the (S,S)-dipeptide aldehydes relative to the (R,S) analogs, an observation which can be explained on the basis of three-point binding of the peptides to vanadium. VCH Verlagsgesellschaft mbH, 1996.
